Skip to Navigation
University of Pittsburgh
Print This Page Print this pages

June 11, 2009


Treatments for diabetic heart patients compared

A study by researchers in the Graduate School of Public Health found no difference in mortality among patients with type 2 diabetes and stable heart disease who received prompt bypass surgery or angioplasty compared to drug therapy alone.

The study, which focused exclusively on patients with both conditions, appears in the June 11 issue of the New England Journal of Medicine and was presented at a recent session of the American Diabetes Association.

The researchers also found that while prompt bypass surgery in patients with more severe heart disease did not lower mortality, it lowered their risk of subsequent major cardiac events.

Principal investigator Sheryl F. Kelsey, professor of epidemiology, said, “We began this study because we don’t know how best to treat this deadly duo that is affecting more and more people at increasingly younger ages. Our results provide needed guidance about which approaches can best help these patients.”

The study, coordinated by GSPH’s Epidemiology Data Center, involved 49 clinical sites in the United States and abroad. Results were based on 2,368 patients with both type 2 diabetes and stable heart disease who were under a physician’s care to control their cholesterol and blood pressure. Patients were randomized to receive drug therapy alone or drug therapy in addition to prompt revascularization to restore blood flow — either angioplasty to open blocked arteries or bypass surgery. The study was not a comparison between angioplasty and bypass surgery, but rather a comparison between a prompt procedure and medical therapy alone.
The investigators also looked at which of two diabetes drug treatment strategies resulted in better outcomes — insulin-providing (increasing the amount of insulin) or insulin-sensitizing (lowering the body’s resistance to its own insulin, such as metformin or rosiglitazone).

The results show that five-year survival rates did not differ significantly between the revascularization group (88.3 percent) and the drug therapy group (87.8 percent). In addition, there was no significant difference in survival between those who received insulin-providing drugs (87.9 percent) and those who received insulin-sensitizing drugs (88.2 percent).

However, in the group that received bypass surgery, the rate of all major cardiovascular events (heart attacks, strokes and death) was significantly lower (22.4 percent) compared to those who received drug therapy alone (30.5 percent). This benefit appeared to be greatest in those who underwent bypass and received insulin-sensitizing drugs.

Pitt co-investigators of the study included epidemiology professors Trevor Orchard and Maria Mori Brooks.

Major funders of the study included the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and GlaxoSmithKline.


Emergency room communication research funded

Paul Daniel Patterson, professor in the School of Medicine’s Department of Emergency Medicine, has received a $10,000 grant from the American Society for Healthcare Risk Management Foundation.

The grant will help fund Patterson’s research proposal, “The Effect of Communication Patterns in the Emergency Department on Quality and Performance.”


Grant awarded for plant diversity study

Tia-Lynn Ashman, professor of plant evolutionary ecology in the Department of Biological Sciences, has been awarded an international planning grant of more than $19,000 from the National Science Foundation.

She will collaborate with two scientists from the Estación Biológica de Doñana in Seville, Spain, on a project to study the relationship between plant-pollinator interactions and biodiversity. The work will take advantage of a hotspot of plant diversity in the Baetic mountain ranges of southern Spain.

The planning grant will fund joint feasibility studies enabling the researchers to gather preliminary data needed to design and implement experiments to test hypotheses about the mechanisms that underlie global pollen limitation-biodiversity gradients.
The ultimate research objective is to determine the response of pollination and pollen limitation of plant reproduction to increasing diversity across a wide range of plant community diversities and determine whether this relationship differs for endemic plants.


Diabetes research progresses

Building on findings from earlier this year, a research team led by Andrew F. Stewart, professor of medicine and chief of the Division of Endocrinology and Metabolism, has shown in mouse experiments that knocking out two cell cycle proteins leads to robust replication of insulin-producing beta cells. The results were presented recently at a meeting of the American Diabetes Association and in a paper published online in the ADA’s journal Diabetes.

Stewart said, “These proteins act like brakes to prevent regeneration of beta cells. It’s a redundant system, though, so removing just one of the proteins isn’t sufficient to make beta cells replicate.”

In earlier studies, endocrinology professor Rupangi Vasavada, working with Stewart, assessed mice that lacked a key regulator of cell division called retinoblastoma protein (pRB), but the loss of pRB alone did not make beta cells regenerate.

In the current study, lead author George Harb, postdoctoral fellow in endocrinology, engineered mice to lack the gene for a similar cell cycle protein called p130, but there was no impact on beta cell production. His next step was to engineer mice deficient in both proteins, which resulted in a marked increase in beta cell replication.

Stewart noted, “The cell cycle has yet another protein, called p107, that is much like pRB and p130. Now we want to see what happens to beta cell numbers if we knock out any two of the three or all three.”

In an online publication in Diabetes in January, another of his research teams showed that human beta cells could be induced to replicate by boosting levels of cell cycle proteins cdk-6 and cyclin D1 using gene therapy techniques. When study co-author Nathalie Fiaschi-Taesch, professor in Pitt’s endocrinology division, transplanted those engineered cells into diabetic mice, blood sugar levels normalized.

The Pitt researchers also plan to examine the effects of gain or loss of other cell cycle proteins to identify targets that might make it possible to treat diabetes by giving patients more insulin-producing cells. “It’s now clear that both type 1 and type 2 diabetes are beta cell deficiency diseases,” Stewart said. “And while we work on making more beta cells, our colleagues are trying to tackle the autoimmunity problems that cause a reduction in their number. Ultimately, both issues have to be addressed to develop a cure for diabetes.”

The research was supported by grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation (JDRF), and the Don and Arleen Wagner and the Pam and Scott Kroh family foundations. Harb also is supported by a JDRF fellowship award.


Funds awarded for anthrax research

Saleem Khan, professor in the School of Medicine’s microbiology and molecular genetics department, has been awarded a $416,625 National Institute of Allergy and Infectious Diseases grant for “Role of RepX Protein in Replication/Partitioning of Anthrax Toxin Plasmid pXO1.”

The two-year research project will identify the domains of RepX protein important in its replication and segregation activities as well as genes involved in the copy number control and stability of the pXO1 plasmid in Bacillus anthracis. The research also will identify the cellular proteins that interact with the RepX protein and co-localize RepX and pXO1 DNA in vivo.

The proposed studies could lead to a better understanding of the elements involved in the stable replication and maintenance of the pXO1 plasmid and may contribute to the future development of plasmid-specific co-therapeutic drugs that can reduce the virulence of B. anthracis and related organisms.


Mini surgery aids esophageal cancer patients

Patients with esophageal cancer who require surgery may benefit from having minimally invasive surgery instead of an open esophagectomy, or removal of the esophagus, according to a University of Pittsburgh Cancer Institute (UPCI) phase II study sponsored by the National Institutes of Health.

Lead investigator James D. Luketich, professor of surgery at the School of Medicine and co-director of UPCI’s lung and esophageal cancer program, said esophageal cancer rates have risen more than 400 percent in the past 20 years, the most rapid increase among all cancers.

Single-institution studies previously have demonstrated success with minimally invasive esophagectomies (MIE). This multi-center study enrolled 106 patients from 16 institutions across the country. Of those patients, 99 qualified for and received an MIE. While overall survival rates remained the same whether a patient received an MIE or an open procedure, surgical mortality rates were lower and the hospital stays shorter for MIE patients.

Co-investigator and professor of surgery Arjun Pennathur presented the work at a recent meeting of the American Society of Clinical Oncology. He said, “The best treatment for this disease is removal of the tumor, and if we can do the necessary surgery with MIE and reduce recovery times and mortality rates, then patients will benefit enormously.”

Luketich added, “With this cancer on the rise, we need to do everything we can to increase patients’ survival. MIE is an ideal surgery because it encourages faster healing and less time spent inside the hospital, where patients can be exposed to infections and other complications. The more quickly patients recover, the more quickly they can begin other forms of treatment they might need.”


Sustainability research funded

The Mascaro Center for Sustainable Innovation recently awarded three research grants to Pitt faculty members.

• Mark Kimber of mechanical engineering and materials science was awarded $34,280 for “Environmental Impact and Energy Efficiency of Liquid Cooled Data Centers.”

• Bong Jae Lee of mechanical engineering and materials science and Albert C. To of civil and environmental engineering were awarded $46,446 for “Multiscale Multifunctional Bandgap Structured Materials for Sustainable Buildings.”

• Steven P. Levitan of electrical and computer engineering and Donald M. Chiarulli of computer science were awarded $50,556 for “Building Information Modeling for Sustainability.”


Blacks more likely to want life-extending treatment

When faced with a terminal illness, African-American seniors were two times more likely than whites to say they would want life-prolonging treatments, according to a Pitt study funded by the National Institute on Aging.

The study, led by Amber E. Barnato, professor of medical, clinical and translational science and health policy, was based on interviews and surveys with more than 2,800 Medicare beneficiaries age 65 and older, making it the largest nationally representative sample of U.S. seniors’ end-of-life treatment preferences.

The research is available online at and in the June issue of the Journal of General Internal Medicine.

Overall, the majority of Medicare beneficiaries surveyed preferred not to die in a hospital or to receive life-sustaining measures at the end of life. When asked about their treatment preferences in the event they were diagnosed with a terminal illness and had less than a year to live, more African Americans (18 percent) than whites (8 percent) reported that they would prefer to die in a hospital.

African Americans (28 percent) also were more likely than whites (15 percent) to report that they would opt for life-prolonging drugs, even if the treatment made them feel worse all of the time.

Only 49 percent of African Americans compared to 74 percent of whites responded that they would want potentially life-shortening palliative drugs (for pain and comfort only).

Lastly, when asked whether they would opt for mechanical ventilation to extend their lives for a week, 24 percent of African Americans said they would, compared to 13 percent of whites. When mechanical ventilation would extend life by one month, this percentage rose to 36 percent in African Americans, compared to 21 percent in whites.

“We collected detailed information about personal and social factors that might explain the relationship between African Americans and preference for more intensive end-of-life treatment,” said Barnato. “An overly optimistic view of the ability of mechanical ventilation, a breathing machine, to save lives and return people to their normal activities explained some, but not all, of this difference.”

Although the study looked at differences in treatment preferences by race, Barnato cautions it should not be viewed as an invitation to generalize. “As doctors, we should ask each patient and family about their goals of treatment, then offer the treatments that meet those goals, rather than making assumptions about treatment preferences based on race,” she said.


Genes help predict response to melanoma treatment

University of Pittsburgh Cancer Institute (UPCI) researchers have identified eight genes that help predict a melanoma patient’s response to treatment. The findings recently were presented to the American Society of Clinical Oncology.

Principal investigator Hussein Tawbi, professor of medicine in the medical school and researcher in UPCI’s melanoma program, said, “Approximately 70,000 people will be diagnosed with metastatic melanoma this year. This form of cancer is aggressive and often resistant to chemotherapy. In fact, only 7-10 percent of patients are likely to respond to the current standard of care. We wanted to see if there was a way to predict which patients would respond to treatment and which ones would not.”

Using neural network analysis, Tawbi and his colleagues examined the tumor tissues of 21 patients with metastatic melanoma, some of whom responded to chemotherapy and some who did not.

The researchers’ survey of more than 25,000 genes and their regulators identified a signature of eight genes and their switches that predict a patient’s likelihood of responding to treatment for metastatic melanoma. The results are being validated in a larger sample of 80 patients.

“The genes that we isolated in this study could be potential targets for new therapies,” explained Tawbi. “We need to find options for the large number of patients with metastatic disease who won’t respond to existing treatments. This work takes us one step closer to doing so,” said Tawbi.

The study was funded by the Eastern Cooperative Oncology Group and UPCI.


Chemo combo slows cancer, fails to increase survival

Patients undergoing treatment for advanced head and neck cancers may respond well to the addition of gefinitib to chemotherapy, according to a study sponsored by the Eastern Cooperative Oncology Group and chaired by Ethan Argiris, professor of medicine and co-leader of the head and neck cancer program of the University of Pittsburgh Cancer Institute.

Gefinitib, which also is known by the trade name Iressa, is a targeted therapy against the epidermal growth factor receptor with fewer side effects than traditional chemotherapies.

“We found that adding gefinitib to standard chemotherapy was well tolerated by patients who had already received chemotherapy or were frail,” said Argiris.

“We had hoped this study would improve the survival rate of patients, but while gefinitib did postpone spread of the disease, it did not increase survival rates. The finding that the addition of gefinitib to chemotherapy can delay the growth of head and neck cancer suggests a potential beneficial effect from combination therapy.”

Argiris plans to conduct further studies to identify the subsets of patients most likely to respond to the drug and to examine patients’ quality of life while taking the combination therapy.


Redefine binge drinking for kids, prof says

The criteria used to assess blood alcohol concentrations (BACs) and binge drinking behaviors in children and adolescents should be based on pediatric rather than adult physiology, according to a Pitt study in the June issue of Pediatrics.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recently defined binge drinking as a drinking pattern that brings a person’s BAC to greater than 0.08 grams per deciliter (g/dL), which is a level accompanied by significant physical and mental impairment and the level currently used to define drunk driving in the U.S.

Typically, this means five drinks for a man or four drinks for a woman within a two-hour period. Current standards for BACs and binge drinking in children under 18 are based on adult criteria.

Study author John E. Donovan, professor of psychiatry and epidemiology at the School of Medicine and the Graduate School of Public Health, said, “The NIAAA definition of binge drinking was developed for adults and not for children under 18. Both children and young adolescents weigh substantially less than adults and likely would achieve considerably higher BACs with five drinks within a two-hour period or would reach a BAC greater than 0.08 g/dL with significantly fewer drinks.”

Donovan examined child, adolescent and adult body compositions and alcohol elimination rates from the 1999-2002 national health and nutrition examination survey and used the updated formula to estimate BACs for more than 4,700 children and teens ages 9-17 for alcohol intake levels of one-five standard drinks to determine the number of drinks at each age that led to a BAC of greater than 0.08 g/dL.

These estimations suggest that binge drinking should be defined as three or more drinks for 9-13-year-old children; four or more drinks for boys and three or more drinks for girls ages 14 or 15, and five or more drinks for boys and three or more drinks for girls ages 16 or 17. These results also suggest that the definition for heavy drinking should be modified as well.

“When kids and young teens use alcohol, it puts them at heightened risk for later alcohol and drug dependence, delinquency, early pregnancy and sexually transmitted diseases, as well as involvement in motor vehicle crashes,” added Donovan. “Since considerably fewer drinks are needed to get high BAC levels in children, pediatricians and nurse practitioners who screen kids for alcohol use should intervene at much lower levels of alcohol involvement than previously thought.”

Donovan’s research is funded by grants from the National Institute on Alcohol Abuse and Alcoholism.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

We welcome submissions from all areas of the University. Submit information via email to:, by fax to 412/624-4579 or by campus mail to 308 Bellefield Hall.

For submission guidelines, visit online.

Leave a Reply